Malaria causes more than 2 million deaths each year, mainly in Africa. However, an effective vaccine, which is necessary for sustainable control of the disease, remains elusive. The feasibility of vaccination against malaria has been amply demonstrated using radiation-attenuated sporozoites (RAS), which protect rodents, non-human primates and humans by targeting the sporozoites (which are inoculated into the skin by biting Anopheles mosquitoes) and subsequent liver stages of the parasites. The development of RAS is aborted in the liver and thus these parasites do not progress to disease-inducing blood stage infection (FIG. 1). However, despite the sterilising immunity offered by γ-irradiated parasites, practical issues, including large-scale production and ensuring uniformity of the end product, make it unlikely that this vaccine could be licensed for human use. Nevertheless RAS is a well studied experimental vaccination model in the laboratory. The most dominant immune response in the RAS model is activated by the circumsporozoite surface protein (CSP; FIG. 2). These findings boosted the development of the RTS,S vaccine that is based on the CS protein. To date RTS,S is the most advanced malaria vaccine on the market, it is currently in clinical phase III. Studies with healthy volunteers and African children living in endemic areas showed good tolerance and safety of the vaccine. However, the efficacy of RTS,S, also with different adjuvant systems, is only 40-60%. Additionally observations in CS transgenic mice showed that protection could be observed also in mice that are tolerant to CSP, which indicates the presence of other antigens inducing the immune response of the host. Studying RAS induced immune responses is always limited by the fact that the genetic background of injected sporozoites highly varies between individual sporozoites and also between different batches of sporozoites resulting also in differently expressed antigens. Recent advances in gene targeting technology have facilitated the generation of genetically attenuated parasites (GAP) that harbour defined mutations in genes essential for parasite development. Like RAS, GAP are attenuated in the liver and thereby confer to a stage specific sterile immunity, but GAP are arrested at a specific time point (˜24 hours) following initiation of infection and at a very specific stage of differentiation (FIG. 1). In contrast, RAS harbour multiple, heterogeneous mutations and growth arrest occurs at multiple stages. The well-defined genetically attenuated parasites (uis3(−) and/or uis4(−)) are therefore ideal tools for further characterisation of the protective immune responses to liver stage parasites. Studies in knock-out mice showed that Interferon-γ producing T lymphocytes mediate the GAP induced immunity and that B cells are not important. A closer look even revealed CD8+ T cells to be the major player. However, the antigenic specificities and effector mechanisms involved in that immunity are not yet understood.
It was an object of the present invention to provide means for an effective malaria vaccine. More specifically, it was an object of the present invention to identify novel antigens that are critical for immunity.